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A One Health Study of Monkeypox: Human Infection, Animal Reservoir, Disease Ecology, and Diagnostic Tools

A One Health Study of Monkeypox: Human Infection, Animal Reservoir, Disease Ecology, and Diagnostic Tools

This study is led by Professor Arnaud Fontanet, Director of the Emerging Diseases Epidemiology unit at the Institut Pasteur, who also heads the AFRIPOX project on the same topic. Alexandre Hassanin, an evolutionary zoologist specializing in tropical mammals at the Institut de SYstématique, Évolution, Biodiversité (Paris, France), is assisting Professor Fontanet with the taxonomic identification of animal hosts and phylogeographic analyses. Nicolas Berthet and Antoine Gessain, virologists specializing in emerging viruses at the Institut Pasteur de Paris, and Alexandre Hassanin, are assisting Professor Fontanet with the Phylogenetic analysis of virus strains.

Duration of the project : 2020-2024 (currently underway)

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Monkeypox, an emerging Orthopoxvirus with a similar disease presentation to smallpox, is a zoonotic virus which can spread from person to person. Although to date, monkeypox events have erupted in West and Central African rainforests, their frequency, size, and geographic scope have expanded substantially in recent years. Imported cases have been detected in multiple locations, including Europe. Yet many aspects of this emerging infectious disease remain unclear, including its animal reservoir, its risk factors for zoonotic and interhuman transmission, and ecological characteristics that may facilitate monkeypox emergence. Consequently, the 2018 WHO Research & Development Blueprint designated monkeypox as an emerging disease requiring “accelerated research & development and public health action”. The AFRIPOX collaboration will mobilize an international, multidisciplinary One Health partnership spanning epidemiology, anthropology, zoology, environmental ecology, virology and mathematical modelling to tackle four research objectives investigating monkeypox at the human-animal-ecosystem interface.

The research engineer recruited for this multidisciplinary project will analyze DNA sequences from the animal species hosting the virus in order to test the hypothesis of co-evolution between the virus and its reservoir host.

In collaboration with the other project teams, the research engineer will analyze the genetic sequences of viruses isolated from infected animals and humans in order to:

  • Identify the animal reservoir and secondary hosts of monkeypox in areas of Central Africa where monkeypox is known to circulate 
  • Understand the relationships and differences between the viral strains circulating in human and animal populations  

Identifying the animal species involved in the emergence of monkeypox and the geographical distribution of these species will help to pinpoint zones at risk of zoonotic spillover and enhance outbreak preparedness activities. Describing phylogenetic links between human cases and/or possible animal cases will help to better understand how monkeypox circulates in Central Africa. A better understanding of the emergence of human epidemics is essential to control the disease. 

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Related Articles

 

Monkeypox is an emerging infectious disease, which has a clinical presentation similar to smallpox. In this report, the researchers described the first 10 monkeypox virus genomes sequenced from human cases identified in the Central African Republic (CAR) between 2001 and 2018.

The results indicate that the CAR isolates belong to three lineages closely related to those found in the Democratic Republic of the Congo, and that they emerged in the rainforest block of the Congo Basin.

Since most human index cases in CAR occurred at the edge of rainforests, transmissions from wild forest mammals is the most likely hypothesis.

Molecular dating estimates suggest that periods of intense political instability resulting in population movements within the country, often associated also with increased poverty, may have led to more frequent contact with host wild animals.

Berthet N., Descorps-Declère S., Besombes C., Curaudeau M., Nkili Meyong A.A., Selekon B., Labouba I., Gonofio E.C., Ouilibona R.S., Simo Tchetgna H.D., Feher M., Fontanet A., Kazanji M., Manuguerra J.C., Hassanin A., Gessain A. & Nakoune E. (2021). Genomic history of human monkey pox infections in the Central African Republic between 2001 and 2018. Scientific reports 11: 13085.

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To date, viruses closely related to SARS-CoV-2, the causal agent of the COVID-19 pandemic, have been reported in four bat species of the genus Rhinolophus (R. acuminatus, R. affinis, R. malayanus, and R. shameli).

In this report, the dispersal capacity of these bat species was studied using genetic data, and the results were used to better predict the ecological niche of bat coronaviruses closely related to SARS-CoV-2.  

The analyses show that these coronaviruses have a high probability of occurrence in the four following geographic areas: (i) southern Yunnan, northern Laos and bordering regions in northern Thailand and northwestern Vietnam; (ii) southern Laos, southwestern Vietnam, and northeastern Cambodia; (iii) the Cardamom Mountains in southwestern Cambodia and the East region of Thailand; and (iv) the Dawna Range in central Thailand and southeastern Myanmar. By contrast, the researchers found that the ecological niche of bat coronaviruses related to SARS-CoV, the causal agent of the 2002-2004 outbreak of SARS, is mainly restricted to China.

Hassanin A., Tu V.T., Curaudeau M. & Csorba G. (2021) Inferring the ecological niche of bat viruses closely related to SARS-CoV-2 using phylogeographic analyses of Rhinolophus species. Scientific reports 11: 14276.

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An online conference-debate has been organized by the SCOR Foundation for Science, on Thursday, June 2nd 2022, with Professor Arnaud Fontanet who has provided an update on the recent Monkeypox outbreak and on what the experts know about this pandemic. Click here to read more

 

 

2022 Interim Report for the SCOR Foundation
 

click here to read it

This study is led by Professor Arnaud Fontanet, Director of the Emerging Diseases Epidemiology unit at the Institut Pasteur, who also heads the AFRIPOX project on the same topic. The project is expected to run for four years, 2020-2024.

Monkeypox has become a hot topic since the infection started to gain ground in 2022 and now has been reported in countries far beyond its historic range on the African continent. There is also growing evidence to support a possible link between the spread of the virus, population growth and deforestation in the areas of origin of the virus.

Previous epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contact with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts, and the reservoir host has yet to be discovered. 

In this report, the researchers provided a complete list of African mammal genera (and species) in which MPXV was previously detected and predicted the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, they reconstructed the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases and conducted overlap analyses with the ecological niches inferred for 99 mammal species in order to identify the most probable animal reservoir. 

The results indicate that the MPXV niche covers three African rainforests, including the Congo Basin and the Upper and Lower Guinean forests. The most probable MPXV reservoir is Funisciurus anerythrus, an arboreal squirrel, based on the two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection. 

To better understand the evolutionary history of Funisciurus anerythrus, the researchers sequenced full genomic data for a selection of sixteen selected squirrels of the tribe Protoxerini. Both mitochondrial and nuclear phylogenies support a strong phylogeographic structure within Funisciurus anerythrus, with a basal dichotomy separating populations from West Africa from those of Central Africa. Four geographic lineages corresponding to the Upper Guinean forests, the Dahomey Gap, the Lower Guinean forests and the Congo Basin. Since this pattern is very similar to the phylogeography of MPXV, these results provide additional support for a key role of Funisciurus anerythrus as reservoir host of the MPXV.

Article by Antoine Gessain, M.D. Emmanuel Nakoune, Ph.D. and Yazdan Yazdanpanah, M.D. Monkeypox | NEJM